Toward the discovery of life assurance genes, we are performing a screen for extended lifespan in Drosophila melanogaster by single gene mutations. The mutant line methuselah consistently displays an approximately 40 percent increase in average lifespan. Interestingly, the mutant flies also show enhanced resistance to conditions of stress, including starvation, low humidity, and high temperature. Upon exposure to paraquat, a free radical generator, they survive longer than control flies. Excision, along with adjacent DNA, results in embryonic lethality in homozygotes, suggesting that the gene also plays an important role during development. The gene structure predicts a protein sequence containing seven hydrophobic regions with homology to various G-protein-coupled, seven-transmembrane-domain cell receptors. This finding suggests that Drosophila can use signal transduction pathways to modulate stress response and aging. This project is to analyze the mechanism involved in methuselah, and to undertake an expanded project for the isolation and analysis of additional life assurance genes.